Boys and girls show differential susceptibility to diseases such as dyslexia, autism and attention deficit hyperactivity disorder, in part due to differences in brain development. Previous studies suggest that sexual dimorphisms of brain structure and gene expression reflect not only the influence of gonadal hormones, but also direct effects of sex chromosome genes. This project examines differential expression of specific X chromosome genes in male and female mice and their effects on brain development, especially in the cerebral cortex. This objective of this project is to test the hypothesis that differential expression of Xlr3 genes (which encode chromatin binding proteins) regulates neural precursor proliferation, differentiation, migration, downstream gene expression, and morphology. This objective will be accomplished through 3 Specific Aims: (1) analyze the expression of Xlr3 genes in developing male and female brains; (2) identify downstream genes regulated by differential Xlr3 expression; and (3) characterize neurodevelopmental functions of Xlr3 genes through gain- and loss-of-function assays in embryonic cerebral cortex in vivo. This project will thus elucidate gender differences in brain development that may contribute to disease susceptibility. .